Abstract
To compare efficacy and safety outcomes of DWI-FLAIR mismatch versus CT/MR perfusion-based selection for intravenous thrombolysis (IVT) in extended-window acute ischemic stroke (AIS), we performed a systematic review and meta-analysis of randomized controlled trials enrolling adults with acute ischemic stroke treated with imaging-selected IVT beyond 4.5 h from last known well or with unknown onset. Trials using DWI-FLAIR mismatch or CT/MR perfusion selection were included. Outcomes were excellent functional outcome, functional independence, symptomatic intracranial hemorrhage (sICH), parenchymal hematoma, major bleeding, and mortality. Random-effects pairwise meta-analysis and Bucher-type indirect comparison were performed. Eight randomized trials including 2,546 patients were analyzed. Compared with best medical treatment, IVT improved excellent functional outcome (mRS 0-1: RR 1.27, 95% CI 1.14-1.40) and functional independence (mRS 0-2: RR 1.15, 95% CI 1.07-1.23), but increased sICH (RR 5.21, 95% CI 2.25-12.04). In imaging-stratified analyses, functional outcome RRs favored IVT in both perfusion-based and DWI-FLAIR mismatch-selected trials, with wider confidence intervals in the DWI-FLAIR subgroup. Hemorrhagic risk was increased with intravenous thrombolysis in both imaging subgroups, but subgroup interaction testing and a Bucher-type indirect comparison did not detect a statistically significant between-paradigm difference; the indirect comparison re-expresses the subgroup contrast rather than adding independent evidence. In AIS patients not planned for routine endovascular therapy, imaging-selected IVT beyond 4.5 h was associated with improved functional outcomes but increased sICH risk. No definitive superiority or equivalence was established between imaging strategies; imaging choice should be guided by clinical context, time window, EVT eligibility, local workflow, and patient-level factors.